Ultra Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry-Based Metabonomics Reveal Protective Effect of Terminalia chebula Extract on Ischemic Stroke Rats.

Terminalia chebula (TC), a kind of Combretaceae, is a widely used herb in India and East Asia to treat cerebrovascular diseases. However, the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not clear. The present study focused on the effects of TC on metabonomics in a stroke model. Rats were divided randomly into sham, model, and TC groups. Rats in the TC group were intragastrically administered with TC for 7 days after a middle cerebral artery occlusion (MCAO) operation. The sham and the model groups received vehicle for the same length of time. Subsequently, the neuroprotective effects of TC were examined by evaluation of neurological defects, assessment of infarct volume, and identification of biochemical indicators for antioxidant and anti-inflammatory activities. Further, metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically. Consist with the results of biochemical and histopathological assays, pattern recognition analysis showed a clear separation of the model group and the sham group, indicating the recovery impact of TC on the MCAO rats. Moreover, 12 potential biomarkers were identified in the MCAO model group, involving energy (lactic acid, succinic acid, and fumarate), amino acids (leucine, alanine, and phenylalanine), and glycerophospholipid (PC [16:0/20:4], PC [20:4/20:4], LysoPC [18:0], and LysoPC [16:0]) metabolism, as well as other types of metabolism (arachidonic acid and palmitoylcarnitine). Notably, it was found that metabolite levels of TC group were partially reversed to normal. In conclusion, TC could ameliorate MCAO in rats by affecting energy metabolism (glycolysis and the TCA cycle), amino acid metabolism, glycerophospholipid metabolism, and other types of metabolism.